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Evaluation of the nanostructured lipid carriers potential functionalized with folic acid incorporated with rapamycin for breast cancer treatment

Grant number: 17/22758-3
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2018
Effective date (End): December 31, 2021
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Marlus Chorilli
Grantee:Camila Fernanda Rodero
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated scholarship(s):19/18211-4 - Evaluation of the biological activity of vectorized nanostructured lipid systems for delivery of rapamycin in animal model and breast cancer cell line, BE.EP.DR

Abstract

Breast cancer is defined as a malignant epithelial cell tumor that develops in the breast and also is considered as the second most common cancer in the world. It is estimated worldwide incidence of approximately 1.6 million new cases per year. Among the drugs used in therapy, rapamycin is traditionally used as an immunosuppressant, has been shown a potent activity against breast cancer, since it is able to inhibit the mTOR pathway. However, it is a lipophilic drug, for this reason is kidnapped by erythrocytes and it has chemical instability, factor that compromise bioavailability. Thus, its incorporation in NLC functionalized with folic acid is a viable option. Because these systems can protect the drug from degradation, incorporate hydrophobic drugs, increase the time on site, provide more slow and sustained action. The functionalization of CLN with folic acid enables the release of the drug at the target site by binding to folate receptors which are expressed in low amounts by normal cells and in large quantities by tumor cells (ovary, prostate and breast), and for this reason, reducing the side effects of the treatment. In view of the above, the objective of the present work is to develop and characterize CLN functionalized with folic acid for the incorporation of rapamycin and to evaluate the potential in the treatment of breast cancer. The physical-chemical characterization will involve the determination of the encapsulation efficiency of rapamycin using a method based on HPLC, determination of the hydrodynamic, size measurement, polydispersity, zeta potential, transmission electron microscopy, differential scanning calorimetry analysis and thermogravimetric. Further in vitro release studies of the formulations will be conducted. The cellular uptake and location of the systems will be evaluated by confocal microscopy and flow cytometry. Finally, carriers will be evaluated for efficacy in breast cancer therapy by cytotoxicity and animal model studies. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DOS SANTOS, KAREN CRISTINA; DOS REIS, LEIDIANA ROCHA; RODERO, CAMILA FERNANDA; SABIO, RAFAEL MIGUEL; JUNIOR, ALBERTO GOMES TAVARES; GREMIAO, MARIA PALMIRA DAFLON; CHORILLI, MARLUS. Bioproperties, Nanostructured System and Analytical and Bioanalytical Methods for Determination of Rapamycin: A Review. CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY, . (17/22758-3, 18/23430-4)
DOS SANTOS, KAREN CRISTINA; DOS REIS, LEIDIANA ROCHA; RODERO, CAMILA FERNANDA; SABIO, RAFAEL MIGUEL; JUNIOR, ALBERTO GOMES TAVARES; GREMIAO, MARIA PALMIRA DAFLON; CHORILLI, MARLUS. Bioproperties, Nanostructured System and Analytical and Bioanalytical Methods for Determination of Rapamycin: A Review. CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY, v. 52, n. 5, p. 9-pg., . (18/23430-4, 17/22758-3)
MARENA, GABRIEL DAVI; DOS SANTOS RAMOS, MATHEUS APARECIDO; CARVALHO, GABRIELA CORREA; DE LIMA, LAURA CAMINITTI; CARNEIRO SOARES DO NASCIMENTO, ANDRE LUIZ; SABIO, RAFAEL MIGUEL; RODERO, CAMILA FERNANDA; SPOSITO, LARISSA; BAUAB, TAIS MARIA; CHORILLI, MARLUS. Development and characterization of an amphotericin B - loaded nanoemulsion applied to Candida auris biofilms control. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 74, p. 14-pg., . (19/26821-7, 18/25377-3, 19/09597-6, 19/09831-9, 18/23442-2, 14/50928-2, 17/22758-3, 18/23357-5)
VICTORELLI, FRANCESCA DAMIANI; RODERO, CAMILA FERNANDA; LUTZ-BUENO, VIVIANE; CHORILLI, MARLUS; MEZZENGA, RAFFAELE. Amyloid Fibrils Enhance the Topical Bio-Adhesivity of Liquid Crystalline Mesophase-Based Drug Formulations. ADVANCED HEALTHCARE MATERIALS, v. N/A, p. 9-pg., . (17/22758-3)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
RODERO, Camila Fernanda. Evaluation of the potential of nanostructured lipid carriers functionalized with folic acid for incorporation of rapamycin in the treatment of breast cancer. 2021. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara Araraquara.

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